Project Summary: Human Alcohol Seeking Despite Aversion Prolonged alcohol use results in neuroadaptations leading to decreased sensitivity to alcohol, a shift from positive to negative reinforcement-based alcohol use, increased negative affect that drives further consumption, and, ultimately, aversion-resistant drinking. Aversion resistant drinking is a hallmark of more severe and treatment-resistant persistent alcohol use. It has been widely studied in animal models, but has not been well characterized in humans. This project aims to develop an objective measure of aversion resistant drinking in humans, modeled as alcohol self-administration despite aversion, and to characterize its underlying neural signatures. The positive impact of this project will be to advance the translation between preclinical models and clinical models, and to elucidate distinct mechanisms underlying alcohol use disorder progression in humans.